In preliminary studies, evidence has been generated that complement-granulocyte interactions--specifically C5a-induced granulocyte aggregation and leukoembolization--are previously unsuspected mediators of immune tissue injury. We have demonstrated that such phenomena underlie the neutropenia of hemodialysis and filtration leukapheresis by provoking pulmonary sequestration of PMNs. By nephelometric techniques we have demonstrated PMN aggregation in vitro, and provided thereby a sensitive assay for C5a; more recently, we have demonstrated PMN aggregation and embolization of aggregates in experimental animals using intravital microscopy. In the present study, I propose to pursue these findings in several ways: (a) Study the clearance of added C5a from the circulation, using PMN aggregometry as the assay; (b) Study pharmacologic manipulation of both in vitro and in vivo C-PMN interactions (early studies have already shown an effect of corticosteroids); (c) Continue evaluation of plasma samples from patients with clinical syndromes in which we suspect these mechanisms to be operative--specifically patients with known immuno-hematologic diseases, as well as those with endothelium-damaging diseases such as "shock lung" in which we postulate a role for immune mechanisms; (d) Pursue an initial observation that certain lipids, notably cholesterol and several of its esters derived from atherosclerotic plaques activate complement, induce granulocyte aggregating activity and possibly thereby amplify ischemic damage in atherosclerosis.